HIV-1 entry is initiated by binding of the viral envelope glycoprotein (Env) gp120 to cellular receptor CD4. The interaction results in extensive conformational rearrangements of gp120 and subsequently gp41 after engagement of a coreceptor (either CCR5 or CXCR4). The structural rearrangements of Envs and the interplay between Envs and the cellular receptor and co-receptor bring viral membrane toward target cell membrane, and eventually cause membrane fusion and viral entry. CD4 and envelope glycoprotein gp120 are, therefore, attractive molecular targets for HIV treatment.
Recombinant solubly expressed CD4 (sCD4) containing either all four (T4) or the first two extracellular domains (D1D2) can be used to inhibit HIV-1 entry. Similarly, anti-gp120 antibodies can be used to inhibit HIV infection. Still, there remains a need for new and effective anti-HIV therapies.